Young Morag J
Prince Henry's Institute of Medical Research, Clayton, Australia.
Curr Opin Nephrol Hypertens. 2008 Mar;17(2):174-80. doi: 10.1097/MNH.0b013e3282f56854.
This review addresses the growing area of cardiovascular mineralocorticoid responses and highlights recent work investigating the underlying mechanisms that regulate mineralocorticoid receptor activation and translate mineralocorticoid receptor signaling into cardiac inflammation and fibrosis.
Mineralocorticoid receptor activation has been shown to regulate numerous pathways, including the plasminogen activation system and angiotensin II signaling pathways, which encompass both genomic and nongenomic responses. Mineralocorticoid receptor activation has been demonstrated to result in increased tissue oxidative stress and vascular inflammation, while recent studies provide evidence for changes in tissue oxidative stress, in turn regulating mineralocorticoid receptor activation by alternate ligands. These studies suggest possible mechanisms for the protection afforded by mineralocorticoid receptor blockade in the RALES and EPHESUS trials where plasma aldosterone levels were low or normal.
Experimental models of cardiac fibrosis and clinical observations have established mineralocorticoid receptor activation as a key player in the initiation and progression of cardiovascular disease. Studies over the last 12 months address the mechanisms underlying mineralocorticoid receptor-mediated vascular inflammation and cardiac fibrosis and focus on oxidative stress, inflammation and early tissue remodeling, and describe an increasing range of tissue signaling pathways and novel mechanisms of mineralocorticoid receptor activation that contribute to the pathology of cardiac fibrosis.
本综述探讨心血管盐皮质激素反应这一不断发展的领域，并重点介绍近期有关调节盐皮质激素受体激活以及将盐皮质激素受体信号转化为心脏炎症和纤维化的潜在机制的研究工作。
盐皮质激素受体激活已被证明可调节多种途径，包括纤溶酶原激活系统和血管紧张素II信号通路，这些途径涵盖基因组和非基因组反应。盐皮质激素受体激活已被证实会导致组织氧化应激增加和血管炎症，而近期研究为组织氧化应激的变化提供了证据，进而通过替代配体调节盐皮质激素受体激活。这些研究提示了在血浆醛固酮水平低或正常的RALES和EPHESUS试验中盐皮质激素受体阻断所提供保护作用的可能机制。
心脏纤维化的实验模型和临床观察已确定盐皮质激素受体激活是心血管疾病发生和发展的关键因素。过去12个月的研究探讨了盐皮质激素受体介导的血管炎症和心脏纤维化的潜在机制，重点关注氧化应激、炎症和早期组织重塑，并描述了越来越多的组织信号通路以及盐皮质激素受体激活的新机制，这些机制促成了心脏纤维化的病理过程。
